Predicting the outcome of grade II glioma treated with temozolomide using proton magnetic resonance spectroscopy
Identifieur interne : 000010 ( Pmc/Curation ); précédent : 000009; suivant : 000011Predicting the outcome of grade II glioma treated with temozolomide using proton magnetic resonance spectroscopy
Auteurs : R. Guillevin [France] ; C. Menuel [France] ; S. Taillibert [France] ; L. Capelle [France] ; R. Costalat [France] ; L. Abud [France] ; C. Habas [France] ; G. De Marco [France] ; K. Hoang-Xuan [France] ; J. Chiras [France] ; J-N Vallée [France]Source :
- British Journal of Cancer [ 0007-0920 ] ; 2011.
Abstract
This study was designed to evaluate proton magnetic resonance spectroscopy (1H-MRS) for monitoring the WHO grade II glioma (low-grade glioma (LGG)) treated with temozolomide (TMZ).
This prospective study included adult patients with progressive LGG that was confirmed by magnetic resonance imaging (MRI). Temozolomide was administered at every 28 days. Response to TMZ was evaluated by monthly MRI examinations that included MRI with volumetric calculations and 1H-MRS for assessing Cho/Cr and Cho/NAA ratios. Univariate, multivariate and receiver-operating characteristic statistical analyses were performed on the results.
A total of 21 LGGs from 31 patients were included in the study, and followed for at least
The 1H-MRS profile changes more widely and rapidly than tumour volume during the response and relapse phases, and represents an early predictive factor of outcome over 14 months of follow-up. Thus, 1H-MRS may be a promising, non-invasive tool for predicting and monitoring the clinical response to TMZ.
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DOI: 10.1038/bjc.2011.174
PubMed: 21610707
PubMed Central: 3111204
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Menuel</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Neuroradiology, Pitié-Sapêtrière Hospital, Functional Imaging Laboratory, INSERM U678, UPMC University Paris 6, 47-83 Boulevard de l'Hôpital</institution>, 75013 Paris,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Taillibert, S" sort="Taillibert, S" uniqKey="Taillibert S" first="S" last="Taillibert">S. Taillibert</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Neuro-oncology, Pitié Salpêtrière Hospital</institution>, 75013 Paris,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Capelle, L" sort="Capelle, L" uniqKey="Capelle L" first="L" last="Capelle">L. Capelle</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Neuroradiology, Pitié-Sapêtrière Hospital, Functional Imaging Laboratory, INSERM U678, UPMC University Paris 6, 47-83 Boulevard de l'Hôpital</institution>, 75013 Paris,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Costalat, R" sort="Costalat, R" uniqKey="Costalat R" first="R" last="Costalat">R. Costalat</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>UPMC, UMI 209, UMMISCO, University of Paris 6</institution>, 75005 Paris,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>IRD, UMI 209, UMMISCO</institution>, 93143 Bondy cedex,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Abud, L" sort="Abud, L" uniqKey="Abud L" first="L" last="Abud">L. Abud</name><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Department of Neuroradiology, Pitié-Sapêtrière Hospital</institution>, 75013 Paris,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Habas, C" sort="Habas, C" uniqKey="Habas C" first="C" last="Habas">C. Habas</name><affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Department of Neuroradiology, XV-XX Hospital</institution>, 75571 Paris,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="De Marco, G" sort="De Marco, G" uniqKey="De Marco G" first="G" last="De Marco">G. De Marco</name><affiliation wicri:level="1"><nlm:aff id="aff7"><institution>Laboratoire Contrôle Moteur et Mouvement, UFR STAPS Paris X</institution>, 200 Avenue de la République, 92001 Nanterre,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hoang Xuan, K" sort="Hoang Xuan, K" uniqKey="Hoang Xuan K" first="K" last="Hoang-Xuan">K. Hoang-Xuan</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Neuro-oncology, Pitié Salpêtrière Hospital</institution>, 75013 Paris,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Chiras, J" sort="Chiras, J" uniqKey="Chiras J" first="J" last="Chiras">J. Chiras</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Neuro-oncology, Pitié Salpêtrière Hospital</institution>, 75013 Paris,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Vallee, J N" sort="Vallee, J N" uniqKey="Vallee J" first="J-N" last="Vallée">J-N Vallée</name><affiliation wicri:level="1"><nlm:aff id="aff8"><institution>Department of Neuroradiology, Amiens University Medical Center, University of Picardie Jules Vernes</institution>, 80054 Amiens,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21610707</idno><idno type="pmc">3111204</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111204</idno><idno type="RBID">PMC:3111204</idno><idno type="doi">10.1038/bjc.2011.174</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">000010</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000010</idno><idno type="wicri:Area/Pmc/Curation">000010</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000010</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Predicting the outcome of grade II glioma treated with temozolomide using proton magnetic resonance spectroscopy</title><author><name sortKey="Guillevin, R" sort="Guillevin, R" uniqKey="Guillevin R" first="R" last="Guillevin">R. Guillevin</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Neuroradiology, Pitié-Sapêtrière Hospital, Functional Imaging Laboratory, INSERM U678, UPMC University Paris 6, 47-83 Boulevard de l'Hôpital</institution>, 75013 Paris,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Menuel, C" sort="Menuel, C" uniqKey="Menuel C" first="C" last="Menuel">C. Menuel</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Neuroradiology, Pitié-Sapêtrière Hospital, Functional Imaging Laboratory, INSERM U678, UPMC University Paris 6, 47-83 Boulevard de l'Hôpital</institution>, 75013 Paris,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Taillibert, S" sort="Taillibert, S" uniqKey="Taillibert S" first="S" last="Taillibert">S. Taillibert</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Neuro-oncology, Pitié Salpêtrière Hospital</institution>, 75013 Paris,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Capelle, L" sort="Capelle, L" uniqKey="Capelle L" first="L" last="Capelle">L. Capelle</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Neuroradiology, Pitié-Sapêtrière Hospital, Functional Imaging Laboratory, INSERM U678, UPMC University Paris 6, 47-83 Boulevard de l'Hôpital</institution>, 75013 Paris,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Costalat, R" sort="Costalat, R" uniqKey="Costalat R" first="R" last="Costalat">R. Costalat</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>UPMC, UMI 209, UMMISCO, University of Paris 6</institution>, 75005 Paris,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>IRD, UMI 209, UMMISCO</institution>, 93143 Bondy cedex,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Abud, L" sort="Abud, L" uniqKey="Abud L" first="L" last="Abud">L. Abud</name><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Department of Neuroradiology, Pitié-Sapêtrière Hospital</institution>, 75013 Paris,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Habas, C" sort="Habas, C" uniqKey="Habas C" first="C" last="Habas">C. Habas</name><affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Department of Neuroradiology, XV-XX Hospital</institution>, 75571 Paris,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="De Marco, G" sort="De Marco, G" uniqKey="De Marco G" first="G" last="De Marco">G. De Marco</name><affiliation wicri:level="1"><nlm:aff id="aff7"><institution>Laboratoire Contrôle Moteur et Mouvement, UFR STAPS Paris X</institution>, 200 Avenue de la République, 92001 Nanterre,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hoang Xuan, K" sort="Hoang Xuan, K" uniqKey="Hoang Xuan K" first="K" last="Hoang-Xuan">K. Hoang-Xuan</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Neuro-oncology, Pitié Salpêtrière Hospital</institution>, 75013 Paris,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Chiras, J" sort="Chiras, J" uniqKey="Chiras J" first="J" last="Chiras">J. Chiras</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Neuro-oncology, Pitié Salpêtrière Hospital</institution>, 75013 Paris,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Vallee, J N" sort="Vallee, J N" uniqKey="Vallee J" first="J-N" last="Vallée">J-N Vallée</name><affiliation wicri:level="1"><nlm:aff id="aff8"><institution>Department of Neuroradiology, Amiens University Medical Center, University of Picardie Jules Vernes</institution>, 80054 Amiens,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">British Journal of Cancer</title><idno type="ISSN">0007-0920</idno><idno type="eISSN">1532-1827</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background:</title><p>This study was designed to evaluate proton magnetic resonance spectroscopy (<sup>1</sup>H-MRS) for monitoring the WHO grade II glioma (low-grade glioma (LGG)) treated with temozolomide (TMZ).</p></sec><sec><title>Methods:</title><p>This prospective study included adult patients with progressive LGG that was confirmed by magnetic resonance imaging (MRI). Temozolomide was administered at every 28 days. Response to TMZ was evaluated by monthly MRI examinations that included MRI with volumetric calculations and <sup>1</sup>H-MRS for assessing Cho/Cr and Cho/NAA ratios. Univariate, multivariate and receiver-operating characteristic statistical analyses were performed on the results.</p></sec><sec><title>Results:</title><p>A total of 21 LGGs from 31 patients were included in the study, and followed for at least <italic>n</italic>=14 months during treatment. A total of 18 (86%) patients experienced a decrease in tumour volume with a greater decrease of metabolic ratios. Subsequently, five (28%) of these tumours resumed growth despite the continuation of TMZ administration with an earlier increase of metabolic ratios of 2 months. Three (14%) patients did not show any volume or metabolic change. The evolutions of the metabolic ratios, mean(<italic>Cho</italic>/<italic>Cr</italic>)<sub><italic>n</italic></sub> and mean(<italic>Cho</italic>/<italic>NAA</italic>)<sub><italic>n</italic></sub>, were significantly correlated over time (Spearman <italic>ρ</italic>=+0.95) and followed a logarithmic regression (<italic>P</italic>>0.001). The evolutions over time of metabolic ratios, mean(<italic>Cho</italic>/<italic>Cr</italic>)<sub><italic>n</italic></sub> and mean(<italic>Cho</italic>/<italic>NAA</italic>)<sub><italic>n</italic></sub>, were significantly correlated with the evolution of the mean relative decrease of tumour volume, mean(Δ<italic>V</italic><sub><italic>n</italic></sub>/<italic>V</italic><sub><italic>o</italic></sub>), according to a linear regression (<italic>P</italic><0.001) in the ‘response/no relapse' patient group, and with the evolution of the mean tumour volume (mean<italic>V</italic><sub><italic>n</italic></sub>), according to an exponential regression (<italic>P</italic><0.001) in the ‘response/relapse' patient group. The mean relative decrease of metabolic ratio, mean(Δ(<italic>Cho</italic>/<italic>Cr</italic>)<sub><italic>n</italic></sub>/(<italic>Cho</italic>/<italic>Cr</italic>)<sub><italic>o</italic></sub>), at <italic>n</italic>=3 months was predictive of tumour response over the 14 months of follow-up. The mean relative change between metabolic ratios, mean((<italic>Cho</italic>/<italic>NAA</italic>)<sub><italic>n</italic></sub>−(<italic>Cho</italic>/<italic>Cr</italic>)<sub><italic>n</italic></sub>)/(<italic>Cho</italic>/<italic>NAA</italic>)<sub><italic>n</italic></sub>, at <italic>n</italic>=4 months was predictive of tumour relapse with a significant cutoff of 0.046, a sensitivity of 60% and a specificity of 100% (<italic>P</italic>=0.004).</p></sec><sec><title>Conclusions:</title><p>The <sup>1</sup>H-MRS profile changes more widely and rapidly than tumour volume during the response and relapse phases, and represents an early predictive factor of outcome over 14 months of follow-up. Thus, <sup>1</sup>H-MRS may be a promising, non-invasive tool for predicting and monitoring the clinical response to TMZ.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Brada, M" uniqKey="Brada M">M Brada</name></author><author><name sortKey="Viviers, L" uniqKey="Viviers L">L Viviers</name></author><author><name sortKey="Abson, C" uniqKey="Abson C">C Abson</name></author><author><name sortKey="Hines, F" uniqKey="Hines F">F Hines</name></author><author><name sortKey="Britton, J" uniqKey="Britton J">J Britton</name></author><author><name sortKey="Ashley, S" uniqKey="Ashley S">S Ashley</name></author><author><name sortKey="Sardell, S" uniqKey="Sardell S">S Sardell</name></author><author><name sortKey="Traish, D" uniqKey="Traish D">D Traish</name></author><author><name sortKey="Gonsalves, A" uniqKey="Gonsalves A">A Gonsalves</name></author><author><name sortKey="Wilkins, P" uniqKey="Wilkins P">P 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Br J Cancer</journal-id><journal-title-group><journal-title>British Journal of Cancer</journal-title></journal-title-group><issn pub-type="ppub">0007-0920</issn><issn pub-type="epub">1532-1827</issn><publisher><publisher-name>Nature Publishing Group</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">21610707</article-id><article-id pub-id-type="pmc">3111204</article-id><article-id pub-id-type="pii">bjc2011174</article-id><article-id pub-id-type="doi">10.1038/bjc.2011.174</article-id><article-categories><subj-group subj-group-type="heading"><subject>Translational Therapeutics</subject></subj-group></article-categories><title-group><article-title>Predicting the outcome of grade II glioma treated with temozolomide using proton magnetic resonance spectroscopy</article-title><alt-title alt-title-type="running">Predicting glioma outcome by MRS</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Guillevin</surname><given-names>R</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="corresp" rid="caf1">*</xref></contrib><contrib contrib-type="author"><name><surname>Menuel</surname><given-names>C</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Taillibert</surname><given-names>S</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Capelle</surname><given-names>L</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Costalat</surname><given-names>R</given-names></name><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Abud</surname><given-names>L</given-names></name><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Habas</surname><given-names>C</given-names></name><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>De Marco</surname><given-names>G</given-names></name><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author"><name><surname>Hoang-Xuan</surname><given-names>K</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Chiras</surname><given-names>J</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Vallée</surname><given-names>J-N</given-names></name><xref ref-type="aff" rid="aff8">8</xref></contrib><aff id="aff1"><label>1</label><institution>Department of Neuroradiology, Pitié-Sapêtrière Hospital, Functional Imaging Laboratory, INSERM U678, UPMC University Paris 6, 47-83 Boulevard de l'Hôpital</institution>, 75013 Paris,<country>France</country></aff><aff id="aff2"><label>2</label><institution>Department of Neuro-oncology, Pitié Salpêtrière Hospital</institution>, 75013 Paris,<country>France</country></aff><aff id="aff3"><label>3</label><institution>UPMC, UMI 209, UMMISCO, University of Paris 6</institution>, 75005 Paris,<country>France</country></aff><aff id="aff4"><label>4</label><institution>IRD, UMI 209, UMMISCO</institution>, 93143 Bondy cedex,<country>France</country></aff><aff id="aff5"><label>5</label><institution>Department of Neuroradiology, Pitié-Sapêtrière Hospital</institution>, 75013 Paris,<country>France</country></aff><aff id="aff6"><label>6</label><institution>Department of Neuroradiology, XV-XX Hospital</institution>, 75571 Paris,<country>France</country></aff><aff id="aff7"><label>7</label><institution>Laboratoire Contrôle Moteur et Mouvement, UFR STAPS Paris X</institution>, 200 Avenue de la République, 92001 Nanterre,<country>France</country></aff><aff id="aff8"><label>8</label><institution>Department of Neuroradiology, Amiens University Medical Center, University of Picardie Jules Vernes</institution>, 80054 Amiens,<country>France</country></aff></contrib-group><author-notes><corresp id="caf1"><label>*</label>E-mail: <email>remy.guillevin@psl.aphp.fr</email></corresp></author-notes><pub-date pub-type="ppub"><day>07</day><month>06</month><year>2011</year></pub-date><pub-date pub-type="epub"><day>24</day><month>05</month><year>2011</year></pub-date><volume>104</volume><issue>12</issue><fpage>1854</fpage><lpage>1861</lpage><history><date date-type="rev-recd"><day>18</day><month>04</month><year>2011</year></date><date date-type="accepted"><day>20</day><month>04</month><year>2011</year></date></history><permissions><copyright-statement>Copyright © 2011 Cancer Research UK</copyright-statement><copyright-year>2011</copyright-year><copyright-holder>Cancer Research UK</copyright-holder></permissions><abstract><sec><title>Background:</title><p>This study was designed to evaluate proton magnetic resonance spectroscopy (<sup>1</sup>H-MRS) for monitoring the WHO grade II glioma (low-grade glioma (LGG)) treated with temozolomide (TMZ).</p></sec><sec><title>Methods:</title><p>This prospective study included adult patients with progressive LGG that was confirmed by magnetic resonance imaging (MRI). Temozolomide was administered at every 28 days. Response to TMZ was evaluated by monthly MRI examinations that included MRI with volumetric calculations and <sup>1</sup>H-MRS for assessing Cho/Cr and Cho/NAA ratios. Univariate, multivariate and receiver-operating characteristic statistical analyses were performed on the results.</p></sec><sec><title>Results:</title><p>A total of 21 LGGs from 31 patients were included in the study, and followed for at least <italic>n</italic>=14 months during treatment. A total of 18 (86%) patients experienced a decrease in tumour volume with a greater decrease of metabolic ratios. Subsequently, five (28%) of these tumours resumed growth despite the continuation of TMZ administration with an earlier increase of metabolic ratios of 2 months. Three (14%) patients did not show any volume or metabolic change. The evolutions of the metabolic ratios, mean(<italic>Cho</italic>/<italic>Cr</italic>)<sub><italic>n</italic></sub> and mean(<italic>Cho</italic>/<italic>NAA</italic>)<sub><italic>n</italic></sub>, were significantly correlated over time (Spearman <italic>ρ</italic>=+0.95) and followed a logarithmic regression (<italic>P</italic>>0.001). The evolutions over time of metabolic ratios, mean(<italic>Cho</italic>/<italic>Cr</italic>)<sub><italic>n</italic></sub> and mean(<italic>Cho</italic>/<italic>NAA</italic>)<sub><italic>n</italic></sub>, were significantly correlated with the evolution of the mean relative decrease of tumour volume, mean(Δ<italic>V</italic><sub><italic>n</italic></sub>/<italic>V</italic><sub><italic>o</italic></sub>), according to a linear regression (<italic>P</italic><0.001) in the ‘response/no relapse' patient group, and with the evolution of the mean tumour volume (mean<italic>V</italic><sub><italic>n</italic></sub>), according to an exponential regression (<italic>P</italic><0.001) in the ‘response/relapse' patient group. The mean relative decrease of metabolic ratio, mean(Δ(<italic>Cho</italic>/<italic>Cr</italic>)<sub><italic>n</italic></sub>/(<italic>Cho</italic>/<italic>Cr</italic>)<sub><italic>o</italic></sub>), at <italic>n</italic>=3 months was predictive of tumour response over the 14 months of follow-up. The mean relative change between metabolic ratios, mean((<italic>Cho</italic>/<italic>NAA</italic>)<sub><italic>n</italic></sub>−(<italic>Cho</italic>/<italic>Cr</italic>)<sub><italic>n</italic></sub>)/(<italic>Cho</italic>/<italic>NAA</italic>)<sub><italic>n</italic></sub>, at <italic>n</italic>=4 months was predictive of tumour relapse with a significant cutoff of 0.046, a sensitivity of 60% and a specificity of 100% (<italic>P</italic>=0.004).</p></sec><sec><title>Conclusions:</title><p>The <sup>1</sup>H-MRS profile changes more widely and rapidly than tumour volume during the response and relapse phases, and represents an early predictive factor of outcome over 14 months of follow-up. Thus, <sup>1</sup>H-MRS may be a promising, non-invasive tool for predicting and monitoring the clinical response to TMZ.</p></sec></abstract><kwd-group><kwd>MRI</kwd><kwd><sup>1</sup>H-MRS</kwd><kwd>low-grade glioma</kwd><kwd>temozolomide</kwd><kwd>tumour response</kwd></kwd-group></article-meta></front><floats-group><fig id="fig1"><label>Figure 1</label><caption><p>Evolutions over the time of the metabolic ratios and tumour volume in a patient treated with temozolomide, with a sustained response over 12 months without relapse. Note the great and rapid decrease of the metabolic ratios, compare with the low and delayed decrease of tumour volume.</p></caption><graphic xlink:href="bjc2011174f1"></graphic></fig><fig id="fig2"><label>Figure 2</label><caption><p>Evolutions over the time of the metabolic ratios and tumour volume in a patient treated with temozolomide, with a brief response and then relapse, over the time of follow-up. Note the great and rapid changes of the metabolic ratios in both phases, compare to the low and delayed change of tumour volume; (the minimum extremum points of the convex metabolic curves are observed at 8 month follow-up, and of the convex volumetric curve at 10 month follow-up).</p></caption><graphic xlink:href="bjc2011174f2"></graphic></fig><fig id="fig3"><label>Figure 3</label><caption><p>A series of FLAIR images from the patient from <xref ref-type="fig" rid="fig2">Figure 2</xref>, together with the spectrum at long TE. The data demonstrate a reduction in tumour volume during the response phase to temozolomide. The images displayed are (<bold>A</bold>) at 1 month, (<bold>B</bold>) 3 months, (<bold>C</bold>) 6 months, (<bold>D</bold>) 8 months after the first dose, corresponding to the tumoural metabolism activity before tumour regrowth, and (<bold>E</bold>) at 12 months.</p></caption><graphic xlink:href="bjc2011174f3"></graphic></fig><fig id="fig4"><label>Figure 4</label><caption><p>Mean relative change in tumour volume, mean(Δ<italic>V</italic><sub><italic>n</italic></sub>/<italic>V</italic><sub><italic>o</italic></sub>), for each pattern of response to temozolomide, over the period of follow-up.</p></caption><graphic xlink:href="bjc2011174f4"></graphic></fig><fig id="fig5"><label>Figure 5</label><caption><p>The evolutions of the metabolic ratios, mean(<italic>Cho</italic>/<italic>Cr</italic>)<sub><italic>n</italic></sub> and mean(<italic>Cho</italic>/<italic>NAA</italic>)<sub><italic>n</italic></sub>, were significantly correlated over time (Spearman <italic>ρ</italic>=+0.95) and followed a logarithmic regression (<italic>Y</italic>=1091+1553 × ln(<italic>X</italic>); <italic>R</italic><sup>2</sup>=0.926, <italic>P</italic><0.001).</p></caption><graphic xlink:href="bjc2011174f5"></graphic></fig><fig id="fig6"><label>Figure 6</label><caption><p>In the ‘response/no relapse' patient group, the evolutions over time of metabolic ratios, mean(<italic>Cho</italic>/<italic>Cr</italic>)<sub><italic>n</italic></sub> and mean(<italic>Cho</italic>/<italic>NAA</italic>)<sub><italic>n</italic></sub>, were significantly correlated with the evolution of the mean relative decrease of tumour volume, mean(Δ<italic>Vn</italic>/<italic>V</italic><sub><italic>o</italic></sub>), according to a linear regression (<italic>Y</italic>=0451–0245 × <italic>X</italic>, <italic>R</italic><sup>2</sup>=0971, <italic>P</italic><0.001 and <italic>Y</italic>=0488–0221 × <italic>X</italic>, <italic>R</italic><sup>2</sup>=0986, <italic>P</italic><0.001, respectively).</p></caption><graphic xlink:href="bjc2011174f6"></graphic></fig><fig id="fig7"><label>Figure 7</label><caption><p>In the ‘response/relapse' patient group, the evolutions over time of metabolic ratios, mean(<italic>Cho</italic>/<italic>Cr</italic>)<sub><italic>n</italic></sub> and mean(<italic>Cho</italic>/<italic>NAA</italic>)<sub><italic>n</italic></sub>, were significantly correlated with the evolution of the mean tumour volume (mean<italic>V</italic><sub><italic>n</italic></sub>), according to an exponential regression (<italic>Y</italic>=36495.648 × <italic>e</italic><sup>(0.577 × <italic>X</italic>)</sup>, <italic>P</italic><0.001 and <italic>Y</italic>=35161.045 × <italic>e</italic><sup>(0.602 × <italic>X</italic>)</sup>, <italic>P</italic><0.001, respectively).</p></caption><graphic xlink:href="bjc2011174f7"></graphic></fig><table-wrap id="tbl1"><label>Table 1</label><caption><title>Patient characteristics</title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="char" char="."></col><col align="char" char="."></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50"> </th><th colspan="2" align="center" valign="top" char="." charoff="50"><bold>Number of patients</bold><hr></hr></th></tr><tr><th align="left" valign="top" charoff="50"><bold>Characteristics</bold></th><th align="char" valign="top" char="." charoff="50"><bold><italic>P</italic>=21</bold></th><th align="char" valign="top" char="." charoff="50"><bold>%</bold></th></tr></thead><tbody valign="top"><tr><td align="left" valign="top" charoff="50">Age, median (range), years</td><td colspan="2" align="center" valign="top" char="." charoff="50">43 (32–77)</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td colspan="2" align="center" valign="top" char="." charoff="50"> </td></tr><tr><td colspan="3" align="left" valign="top" charoff="50"><italic>Sex</italic></td></tr><tr><td align="left" valign="top" charoff="50"> Male</td><td align="char" valign="top" char="." charoff="50">7</td><td align="char" valign="top" char="." charoff="50">33</td></tr><tr><td align="left" valign="top" charoff="50"> Female</td><td align="char" valign="top" char="." charoff="50">14</td><td align="char" valign="top" char="." charoff="50">67</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td colspan="3" align="left" valign="top" charoff="50"><italic>Histology</italic></td></tr><tr><td align="left" valign="top" charoff="50"> Oligodendroglioma</td><td align="char" valign="top" char="." charoff="50">14</td><td align="char" valign="top" char="." charoff="50">67</td></tr><tr><td align="left" valign="top" charoff="50"> Oligoastrocytoma</td><td align="char" valign="top" char="." charoff="50">5</td><td align="char" valign="top" char="." charoff="50">24</td></tr><tr><td align="left" valign="top" charoff="50"> Astrocytoma</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">9</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50">Karnofsky score, median (range)</td><td colspan="2" align="center" valign="top" char="." charoff="50">90 (80–100)</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td colspan="3" align="left" valign="top" charoff="50"><italic>Surgery</italic></td></tr><tr><td align="left" valign="top" charoff="50"> Biopsy</td><td align="char" valign="top" char="." charoff="50">12</td><td align="char" valign="top" char="." charoff="50">56</td></tr><tr><td align="left" valign="top" charoff="50"> Resection</td><td align="char" valign="top" char="." charoff="50">9</td><td align="char" valign="top" char="." charoff="50">44</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50">Time interval from diagnosis to onset of TMZ, median (range), months</td><td colspan="2" align="center" valign="top" char="." charoff="50">4 (1–84)</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td colspan="3" align="left" valign="top" charoff="50"><italic>MRI (contrast enhancement)</italic></td></tr><tr><td align="left" valign="top" charoff="50"> Yes</td><td align="char" valign="top" char="." charoff="50">3</td><td align="char" valign="top" char="." charoff="50">14.7</td></tr><tr><td align="left" valign="top" charoff="50"> No</td><td align="char" valign="top" char="." charoff="50">17</td><td align="char" valign="top" char="." charoff="50">81</td></tr></tbody></table><table-wrap-foot><fn id="t1-fn1"><p>Abbreviations: MRI=magnetic resonance imaging; TMZ=temozolomide.</p></fn></table-wrap-foot></table-wrap><table-wrap id="tbl2"><label>Table 2</label><caption><title>Mean (±s.d.) of metabolic ratios and response to treatment</title></caption><graphic xlink:href="bjc2011174t1"></graphic></table-wrap><table-wrap id="tbl3"><label>Table 3</label><caption><title>Spearman's rank correlation coefficients</title></caption><graphic xlink:href="bjc2011174t2"></graphic></table-wrap><table-wrap id="tbl4"><label>Table 4</label><caption><title>Receiver-operating characteristic analysis of <italic>Cho/C</italic><italic>r</italic> with respect to the variable ‘response'</title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50"><bold>Cho/Cr</bold></th><th align="char" valign="top" char="." charoff="50"><bold>Cutoff</bold></th><th align="char" valign="top" char="." charoff="50"><bold>Sensibility (%)</bold></th><th align="char" valign="top" char="." charoff="50"><bold>Specificity (%)</bold></th><th align="char" valign="top" char="." charoff="50"><bold>Area</bold></th><th align="char" valign="top" char="." charoff="50"><bold><italic>P</italic></bold></th></tr></thead><tbody valign="top"><tr><td align="left" valign="top" charoff="50">Response</td><td align="char" valign="top" char="." charoff="50">1.592</td><td align="char" valign="top" char="." charoff="50">66.67</td><td align="char" valign="top" char="." charoff="50">66.67</td><td align="char" valign="top" char="." charoff="50">0.575</td><td align="char" valign="top" char="." charoff="50">0.693</td></tr></tbody></table></table-wrap><table-wrap id="tbl5"><label>Table 5</label><caption><title>Receiver-operating characteristic analysis of (1−(<italic>Cho/Cr/Cho/NAA</italic>)<sub><italic>n</italic></sub>) with respect to the variable ‘relapse'</title></caption><graphic xlink:href="bjc2011174t3"></graphic></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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